Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia |
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| Authors: | Eyal Reinstein Katia Orvin Einav Tayeb‐Fligelman Hadas Stiebel‐Kalish Shay Tzur Allen L. Pimienta Lily Bazak Tuvia Bengal Lior Cohen Dan D. Gaton Concetta Bormans Meytal Landau Ran Kornowski Mordechai Shohat Doron M. Behar |
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| Affiliation: | 1. The Raphael Recanati Genetic Institute, Rabin Medical Center, Israel;2. Sackler School of Medicine, Tel Aviv University, Israel;3. Department of Cardiology, Rabin Medical Center, Israel;4. Department of Biology, Technion‐Israel Institute of Technology, Haifa, Israel;5. Department of Ophthalmology, Rabin Medical Center, Israel;6. Laboratory of Molecular Medicine, Rambam Health Care Campus, Haifa, Israel;7. Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, Israel;8. Genomics Research Center, Gene by Gene, Houston, Texas |
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| Abstract: | We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development. |
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| Keywords: | TAX1BP3 cardiomyopathy Septo‐optic dysplasia exome sequencing |
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